Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial

Int J Chron Obstruct Pulmon Dis. 2015 Jan 29;10:211-21. doi: 10.2147/COPD.S76061. eCollection 2015.

Abstract

Background: There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease.

Methods: Stable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec.

Results: Total cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (-0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (-2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed.

Conclusion: There was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown.

Trial registration: ClinicalTrials.gov NCT01151306.

Keywords: arterial stiffness; chronic obstructive pulmonary disease; statins.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Biomarkers / blood
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Cholesterol / blood
  • Double-Blind Method
  • England
  • Female
  • Forced Expiratory Volume
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Inflammation Mediators / blood
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Pneumonia / blood
  • Pneumonia / diagnosis
  • Pneumonia / drug therapy*
  • Pneumonia / physiopathology
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulse Wave Analysis
  • Simvastatin / adverse effects
  • Simvastatin / therapeutic use*
  • Spirometry
  • Time Factors
  • Treatment Outcome
  • Vascular Stiffness / drug effects*
  • Vital Capacity

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Cardiovascular Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Inflammation Mediators
  • Cholesterol
  • Simvastatin

Associated data

  • ClinicalTrials.gov/NCT01151306